Chapter 31 Mental Disorders

Steven Hyman, Dan Chisholm, Ronald Kessler, , and Harvey Whiteford

Mental disorders are that affect cognition, , Twin studies make it clear that environmental risk factors and behavioral control and substantially interfere both with the also play an important role in mental disorders; concordance for ability of children to learn and with the ability of adults to among identical twins, although substantially higher function in their families, at work, and in the broader . than among nonidentical twins, is still well below 100 percent Mental disorders tend to begin early in life and often run a (Kendler and others 2003). However, as is the case for genetic chronic recurrent course. They are common in all countries factors, investigation of environmental risk factors has proved where their prevalence has been examined. Because of the difficult. For , where nongenetic components of combination of high prevalence, early onset, persistence, and risk may include obstetrical complications and season of birth impairment, mental disorders make a major contribution to (Mortensen and others 1999), perhaps as a proxy for infections total . Although most of the burden attributable early in life, research has been hampered by the modest proven to mental disorders is related, premature mortality, effect of the nongenetic risk factors identified to date. For especially from , is not insignificant. Table 31.1 summa- , , and substance use disorders, where envi- rizes discounted disability-adjusted life years (DALYs) for ronmental risk factors are more robust, adverse circumstances selected psychiatric conditions in 2001. associated with risk, such as early childhood , violence, Mental disorders have complex etiologies that involve inter- poverty, and (Patel and Kleinman 2003) correlate with actions among multiple genetic and nongenetic risk factors. multiple disorders and could be affected by selection bias as well Gender is related to risk in many cases: males have higher rates as by bias associated with self-reporting.Generalizable,prospec- of attention deficit hyperactivity disorder, , and sub- tive cross-cultural studies are needed to delineate nongenetic stance use disorders; females have higher rates of major depres- risk factors more clearly. Posttraumatic stress disorder (PTSD) sive disorder, most anxiety disorders, and eating disorders. is the for which clear environmental triggers are Biochemical and morphological abnormalities of the best documented. Even here, though, enormous interindividual associated with schizophrenia, autism, mood, and anxiety dis- variability occurs in the threshold of stress severity associated orders are being identified using approaches such as post- with PTSD as well as in the evidence from twin studies of genetic mortem analysis and noninvasive neuroimaging. Major world- influences on stress reactivity in triggering PTSD. wide efforts under way to identify risk-conferring genes for The last half of the 20th century saw enormous progress in mental disorders are proving challenging, but initial results are the development of treatments for mental disorders. Beginning promising. Identifying the gene or genes causing or creating in the early 1950s, effective psychotropic were discovered vulnerability for a disorder should help us understand what that treated the symptoms of schizophrenia, , goes wrong in the brain to produce mental illness and should major depression, anxiety disorders, obsessive-compulsive have a clinical effect by contributing to improved diagnostics disorder, attention deficit hyperactivity disorder, and others. and therapeutics (Hyman 2000). The safety and efficacy of , mood-stabilizing,

605 Table 31.1 Disease Burden of Selected Major Psychiatric Disorders, by World Bank Region

World Bank region Sub-Saharan Latin America and Middle East and Europe and East Asia and High-income Africa the Caribbean North Africa Central Asia South Asia the Pacific countries World Total population (millions) 668 526 310 477 1,388 1,851 929 6,159 Total disease burden 344,754 104,287 65,570 116,502 408,655 346,941 149,161 1,535,870 (thousands of DALYs) Total neuropsychiatric 15,151 18,781 8,310 14,106 37,734 42,992 31,230 168,304 disease burden (thousands of DALYs) Total burden (thousands of discounted DALYs per year) Schizophrenia 1,146 1,078 696 778 2,896 3,934 1,115 11,643 Bipolar disorder 1,204 883 567 668 2,237 3,118 1,056 9,733 Depression 3,275 5,219 2,027 4,268 14,582 14,054 8,408 51,833 519 409 264 340 1,081 1,401 536 4,550 Total burden (DALYs per year per 1 million population) Schizophrenia 1,716 2,049 2,247 1,630 2,087 2,126 1,201 1,894 Bipolar disorder 1,803 1,678 1,830 1,400 1,612 1,685 1,137 1,583 Depression 4,905 9,919 6,544 8,944 10,507 7,594 9,054 8,431 Panic disorder 777 777 852 713 779 757 577 740 Percentage of total disease burden Schizophrenia 0.33 1.03 1.06 0.67 0.71 1.13 0.75 0.76 Bipolar disorder 0.35 0.85 0.86 0.57 0.55 0.90 0.71 0.63 Depression 0.95 5.00 3.09 3.66 3.57 4.05 5.64 3.37 Panic disorder 0.15 0.39 0.40 0.29 0.26 0.40 0.36 0.30 Percentage of neuropsychiatric disease burden Schizophrenia 7.56 5.74 8.38 5.52 7.67 9.15 3.57 6.92 Bipolar disorder 7.95 4.70 6.82 4.74 5.93 7.25 3.38 5.78 Depression 21.62 27.79 24.39 30.26 38.64 32.69 26.92 30.80 Panic disorder 3.43 2.18 3.18 2.41 2.86 3.26 1.72 2.70

Source: WHO Global Burden of Disease 2001 estimates recalculated by World Bank region (http://www.fic.nih.gov/dcpp/gbd.html).

, , and drugs have been edge exists to guide treatment. It is particularly unfortunate, established through a large number of randomized clinical therefore, that timely diagnoses and the application of trials. Psychosocial treatments have been developed and tested research-based treatments significantly lag behind the state of using modern methodologies. Brief, symptom-focused psy- knowledge in industrial and developing countries alike. As a chotherapies such as cognitive-behavioral therapies have been result, substantial opportunities exist to decrease the enormous shown to be efficacious for panic disorder, , obsessive- burden attributable to mental disorders worldwide by closing compulsive disorder, and major depression. the gap between what we know and what we do. There is, however, an important caveat about the current Mental disorders are stigmatized in many countries and knowledge base for treatment. As is the case for almost all of cultures (Weiss and others 2001). Stigma has been facilitated , randomized clinical trials have been performed by the slow emergence of convincing scientific explanations for largely with highly selected populations in specialized research the etiologies of mental disorders and by the mistaken belief settings in industrial countries. A need exists to subject existing that symptoms are caused by a lack of will power or reflect some treatments to effectiveness trials in more representative popu- moral taint. Recent scientific findings combined with educa- lations and diverse settings, especially in developing countries. tional efforts in some countries have begun to reduce the stigma That limitation notwithstanding, a substantial body of knowl- (Rahman and others 1998), but shame and associated with

606 | Disease Control Priorities in Developing Countries | Steven Hyman, Dan Chisholm, Ronald Kessler, and others mental illness remain substantial obstacles to help seeking, to fixed false beliefs that are not explained by the person’s culture diagnosis, and to treatment worldwide. The stigmatization of and that the patient holds despite all reasonable evidence to the mental illness has resulted in disparities, compared with other contrary. illnesses, in the availability of care, in research, and in of Patients also exhibit negative symptoms—that is, deficits in the human rights of people with these disorders. normal capacities, such as marked social deficits, impoverish- This chapter focuses on the attributable and avoidable ment of thought and speech, blunting of emotional responses, burden of four leading contributors to mental ill health globally: and lack of motivation. Additionally, patients typically have schizophrenia and related nonaffective psychoses, bipolar cognitive symptoms, such as disorganized or illogical thinking affective disorder (manic-depressive illness), major depressive and an inability to hold goal information in to make disorder, and panic disorder. The choice of these disorders is decisions or plan actions. determined not only by their contribution to disease burden, but also by the availability of data for the cost-effectiveness Natural History and Course analyses. Even where such data are available, they are often from Schizophrenia, as defined in current diagnostic manuals, is industrial countries and extrapolation has been necessary. The almost certainly heterogeneous, but still does not comprise all exclusion of other mental disorders, such as childhood disor- nonaffective psychoses (NAPs). In addition to schizophrenia, ders, from analysis is not because the authors consider these dis- NAPs include schizophreniform disorder,characterized by schiz- orders unimportant but because of the paucity of data.Also, this ophrenia-like symptoms of inadequate duration to qualify as chapter does not specifically deal with the important issue of schizophrenia. Because they cannot be readily disentangled in suicide. A background paper on suicide in developing countries community epidemiological surveys, schizophrenia and other has been developed as part of the Disease Control Priorities NAPs are considered together.Because of the data available,how- Project (DCPP) and is available (Vijayakumar, Nagaraj, and ever, the cost-effectiveness analyses reported below are restricted John 2004). The economic analysis presented in this chapter to schizophrenia. Despite likely etiological heterogeneity, schizo- uses the cost-effectiveness analysis methodology specifically phrenia exhibits consistency in its symptom pattern across those developed for the DCPP. The authors recognize that mental countries and cultures studied (Jablensky and others 1992). disorders impose costs and burdens on families as well as Incidence studies show that onset of schizophrenia and individuals that are not captured by the DALY. Treatment will other NAPs is typically in middle to late adolescence for males alleviate some of this burden in addition to alleviating symp- and late adolescence to early adulthood for females, although toms and disability. later onsets are observed. Childhood-onset cases are quite rare A description of the major clinical features, natural course, but particularly severe (Nicolson and Rapoport 1999). Often, epidemiology, burden, and treatment effectiveness for each schizophrenia is first diagnosed with the occurrence of an group of disorders is given in the next section. For diagnostic episode of florid psychotic symptoms. The first psychotic criteria, readers are referred to The ICD-10 Classification of episode is often preceded by prodromal symptoms such as social Mental and Behavioral Disorders (ICD-10) (WHO 1992) or withdrawal, irritability or dysphoria, increasing academic or Diagnostic and Statistical Manual of Mental Disorders (DSM- work-related difficulties, and increasing . However, IVTR) (American Psychiatric Association 2000). A discussion such symptoms are not specific; studies of whether early diag- follows of population-level costs and cost-effectiveness of inter- nosis and intervention can improve outcomes are under way ventions capable of reducing the current burden associated (McGorry and others 2002). with four disorders in different developing regions of the world The course of schizophrenia is typically one of acute exacer- (tables 31.2–31.6), before moving to a discussion of key issues bations of severe psychotic symptoms, followed by full or par- and implications for policy and improvement of tial . Psychotic episodes may be followed by a full services in developing regions of the world. remission after the first and occasionally other early episodes, but over time, residual symptoms and disability typically con- tinue between (Robinson and others 1999). The time SCHIZOPHRENIA AND NONAFFECTIVE between relapses is markedly extended by maintenance treat- PSYCHOSES ment with antipsychotic drugs, generally at lower doses than are needed to treat acute episodes. Cognitive and occupational Schizophrenia is a chronic disorder punctuated by episodes of functioning tends to decline over the first years of the illness florid psychotic symptoms, such as and delu- and then to plateau at a level that is generally well below what sions. Hallucinations are sensory perceptions that occur in the would have been expected for the individual. Residual impair- absence of appropriate stimuli. Hallucinations may occur in ment, though, has substantial cross-cultural variation for any sensory modality but in schizophrenia are most commonly reasons that are not well understood. Schizophrenia has consis- auditory—for example, hearing voices or noises. are tently been found in epidemiological surveys to be highly

Mental Disorders | 607 comorbid, usually with anxiety disorders, mood disorders, and behavioral approaches to managing specific symptoms and substance use disorders (Kendler and others 1996). improving , group therapy, and family interventions all have demonstrated efficacy in improving clinical outcomes. Community-based models of mental health Epidemiology and Burden care delivery with case management and assertive outreach A great many studies of NAP incidence have been carried out in programs have been shown in health systems of industrial clinical samples. In a review of these studies, Jablensky (2000) countries to be effective ways of managing schizophrenia in the found incidence estimates to be in the range of 0.002 to 0.011 community, for example, by reducing the need for hospital percent per year for schizophrenia and 0.016 to 0.042 percent admissions. However, the applicability of these models to per year for overall NAP. Those annual estimates can be multi- developing countries, as is discussed later, is hard to estimate plied by the number of birth cohorts at risk to yield an estimate because of differences in health system characteristics. Long- of lifetime risk in any one cohort. Assuming conservatively that term remission rates for schizophrenia in developing countries the main age range of risk is between ages 15 and 55, researchers appear to be significantly higher than those reported in indus- estimate lifetime risk is in the range of 0.08 to 0.44 percent for trial countries (Harrison and others 2001), likely resulting from schizophrenia and in the range of 0.64 to 1.68 percent for NAPs. such factors as strong family . Lifetime prevalence estimates from community epidemio- Despite their clear usefulness, current treatments do not logical surveys of NAPs are quite consistent with those from prevent schizophrenia, and no clear evidence demonstrates that clinical studies, in the range of 0.3 to 1.6 percent (see, for exam- they induce full recovery or prevent premature mortality. ple, Hwu, Yeh, and Cheng 1989; Kendler and others 1996). Instead, treatment reduces time in episode of florid Although schizophrenia is a relatively uncommon disorder, and increases time between episodes; thus treatment effects can aggregate estimates of disease burden are high—around 2,000 be understood in terms of improvements in disability. Reported DALYs lost per 1 million total population (table 31.1)— treatment effect sizes from meta-analyses in the literature, con- because the condition is associated with early onset, long dura- verted into improvements in the average level of disability tion, and severe disability. (Andrews and others 2003; Sanderson and others 2004), show improvements (compared with no treatment) of 18 to 19 per- cent (antipsychotic drugs alone) and 30 to 31 percent (antipsy- Interventions chotic drugs with adjunctive psychosocial treatment). Placed A substantial body of evidence exists on the efficacy of various on a disability scale of 0 to 1, where 0 equals no disability, an treatments for schizophrenia and NAP and on the effectiveness “average” case of schizophrenia moves from a disability level of of various models of health care delivery for persons with these 0.63 (untreated weight from the Global Burden of Disease disorders. This evidence comes primarily from industrial coun- study, Murray and Lopez 1996) to 0.43 to 0.54 (treated). tries. The efficacy data show conclusively that antipsychotic drugs reduce severity of the episodes, hasten resolution of florid symptoms, and reduce duration of hospitalization. MOOD DISORDERS Maintenance treatment with antipsychotic drugs prolongs the The cardinal features of mood disorders are pervasive abnor- period between relapses (Joy, Adams, and Lawrie 2001). malities in the predominant emotional state of the person, such A second generation of antipsychotic (also as depressed, elated, or irritable. In mood disorders, these core called atypical) is replacing older neuroleptic antipsychotic emotional symptoms are accompanied by abnormalities in drugs throughout the industrial world. In some clinical trials, physiology, such as changes in patterns of , appetite, and second-generation drugs show small advantages in efficacy energy, and by changes in cognition and behavior. In develop- over first-generation drugs, but their widespread adoption ing countries, concurrent somatic symptoms are also com- results from marked improvement in tolerability. Their relative monly reported and may be the chief complaint. A generally lack of side effects compared with first-generation drugs has accepted subclassification of mood disorders distinguishes led to improved quality of life and improved treatment adher- unipolar depressive disorders from bipolar disorder (defined ence. Second-generation drugs are not without side effects, by the occurrence of ). This distinction is based on however; for example, some are associated with substantial symptoms, course of illness, patterns of familial transmission, weight gain and increased risk of diabetes. One , clozapine, and treatment response. has greater efficacy than other antipsychotic drugs, but because of a 1 percent risk of agranulocytosis, its use requires weekly blood counts and is cumbersome and expensive. Bipolar Disorder Psychosocial interventions also play an important role in Bipolar disorder is characterized by episodes of mania and managing schizophrenia (Bustillo and others 2001). Cognitive- depression, often followed by relative periods of healthy mood

608 | Disease Control Priorities in Developing Countries | Steven Hyman, Dan Chisholm, Ronald Kessler, and others (euthymia). Mixed states with symptoms of both mania and disorder also exhibit chronic psychotic symptoms superim- depression also occur. Mania is typically characterized by posed on their mood . These individuals are said to or irritability, a marked increase in energy, and a have . Their tends to be less decreased need for sleep. Individuals with mania often exhibit favorable than for the usual bipolar patient, although somewhat intrusive, impulsive, and disinhibited behaviors. They may be better than for individuals with schizophrenia. Schizoaffective excessively involved in goal-directed behaviors characterized disorder may also be diagnosed when chronic psychotic symp- by poor judgment; for example, a person might spend all toms are superimposed on unipolar depression. Individuals funds to which he or she has access and more. Self-esteem is with this combination of symptoms have outcomes similar to typically inflated, frequently reaching delusional proportions. patients with schizophrenia (Tsuang and Coryell 1993). Speech is often rapid and difficult to interrupt. Individuals with mania also may exhibit cognitive symptoms; patients can- Epidemiology and Burden. Lifetime and 12-month preva- not stick to a topic and may jump rapidly from idea to idea, lence estimates of bipolar disorder have been reported from a making comprehension of their train of thought difficult. number of community psychiatric epidemiological surveys. Psychotic symptoms are common during manic episodes. The Lifetime prevalence estimates are in the range 0.1 to 2.0 percent depressive episodes of people with bipolar disorder are symp- (Vega and others 1998; Vicente and others 2002), with a tomatically indistinguishable from those who have unipolar weighted mean across surveys of 0.7 percent. Prevalence esti- depressions alone. Unlike anxiety and unipolar mood disor- mates for past-year episodes have a similarly wide range (0.1 to ders, which are more common in women, bipolar disorder has 1.3 percent) (Vega and others 1998) and a weighted mean of an equal gender ratio of lifetime prevalence, although the ratio 0.5 percent. It is important to note that good evidence exists of depressive-to-manic episodes is higher among bipolar suggesting that bipolar disorder has a wide subthreshold spec- women than men. trum that includes people who are often seriously impaired even though they do not meet full DSM or ICD criteria for the Natural History and Course. Retrospective reports from com- disorder (Perugi and Akiskal 2002). This spectrum might munity epidemiological surveys consistently show that bipolar include as much as 5 percent of the general population. The disorder has an early age of onset (in the late teens through mid- ratio of recent-to-lifetime prevalence of bipolar disorder in 20s). Onset in childhood is increasingly recognized, although community surveys is quite high (0.71), indicating that bipolar it remains controversial. Late onset is less common. The vast disorder is persistent. majority of patients with bipolar disorder have recurrent Epidemiological data show that bipolar disorder is associ- episodes of illness, both mania and depression. Classic descrip- ated with substantial impairments in both productive and tions of bipolar disorder suggest recovery to baseline function- social roles (Das Gupta and Guest 2002). Epidemiological evi- ing between episodes, but many patients have residual symp- dence documents consistent delays in patients initially seeking toms that may cause significant impairment (Angst and Sellaro professional treatment (Olfson and others 1998), especially 2000). These states of mania, depression, and lesser (or absent) among early-onset cases, as well as substantial undertreatment symptoms are used in the intervention analysis below. of current cases. Each of these characteristics—chronic, recur- The rate of cycling between mania and depression varies rent course; significant impairments to functioning; modest widely among individuals. One common pattern of illness is treatment rates—contributes to estimates of aggregate disease for episodes initially to be separated by a relatively long period, burden that approach those for schizophrenia (1,200 to 1,800 perhaps a year, and then to become more frequent with age. A DALYs lost per 1 million population, making up more than minority of patients with four or more cycles per year, termed 5 percent of the burden attributable to neuropsychiatric disor- rapid cyclers, tend to be more disabled and less responsive to ders as a whole—see table 31.1). existing treatments. Once cycles are established, most acute episodes start without an identifiable precipitant; the best doc- umented exception is that manic episodes may be initiated by Interventions. Analyses of the primary treatment approaches sleep deprivation, making a regular daily sleep schedule and for bipolar disorder are based on the three health states that avoidance of important in management (Frank, characterize the disorder—mania, depression, and euthymia. Swartz, and Kupfer 2000). Robust evidence from controlled trials shows that antipsychot- Bipolar disorder has consistently been found in epidemio- ic drugs and some produce a relatively rapid logical surveys to be highly comorbid with other psychiatric reduction in symptoms of a manic phase. Mood-stabilizing disorders, especially anxiety and substance use disorders drugs act more slowly, but they reduce the severity and dura- (ten Have and others 2002). The extent of is much tion of acute manic episodes. Maintenance treatment with two greater than for unipolar depressive disorders or anxiety mood-stabilizing drugs— and valproic acid (adminis- disorders. Some individuals with classic symptoms of bipolar tered as sodium valproate)—has been shown to have

Mental Disorders | 609 significant, albeit partial, efficacy in reducing rates of both trating, slow thinking, and poor memory. Psychotic symptoms manic and depressive relapses. The drawback of lithium is that occur in a minority of cases. toxic levels are not much greater than therapeutic levels; thus, serum-level monitoring is required. Natural History and Course. Major depression is an episodic For the cost-effectiveness analyses, lithium and valproic disorder that generally begins early in life (median age of onset acid, which have empirical data supporting their efficacy in in the mid to late 20s in community epidemiological surveys), treating and preventing manic and depressive episodes, were although new onsets can be observed across the lifespan. considered. Because evidence suggests that psychosocial Childhood onset is being increasingly recognized, although not approaches enhance compliance with medication (Huxley, all childhood precursors of adult depression take the form of a Parikh, and Baldessarini 2000), adjuvant strategies also were clear depressive disorder. Most individuals suffering from assessed. The primary treatment effect was a change in the a depressive episode will have a recurrence (Mueller and others population-level disability associated with bipolar disorder (a 1999), with recurrence risk greater among those with early- weighted average of time spent in a manic, depressed, or onset disease. Many individuals do not recover completely euthymic phase of illness). Both an acute treatment effect— from their acute episodes and have chronic milder depression calculated as the product of initial response and reduced punctuated by acute exacerbations (Judd and others 1998). The episode duration—and a prophylactic treatment effect were current term for chronic, milder depression lasting more than ascribed to lithium and valproic acid, resulting in an estimated two years is . Although the symptoms of minor improvement of close to 50 percent over the untreated com- depression are, by definition, less severe than those of a major posite disability weight of 0.445 (Chisholm and others forth- depressive episode, chronicity ultimately makes even this lesser coming). This estimate then was adjusted for expected nonad- form of the illness very disabling in many cases (Judd, Schettler, herence to treatment in real-world clinical settings—slightly and Akiskal 2002). Depression has consistently been found in lower for lithium than for valproic acid (Bowden and others epidemiological surveys to be highly comorbid with other 2000). A secondary effect of treatment—reduction of the case mental disorders, with roughly half the people who have a fatality rate by two-thirds—was also ascribed to lithium, history of depression also having a lifetime . though, because of an absence of current evidence, not to val- of depression and anxiety disorders are genera- proic acid (Goodwin and others 2003). This reduction was lly strongest with generalized anxiety disorder and panic derived through a change in the standardized mortality ratio disorder (Kessler and others 1996). from 2.5 to 1.5, estimated on the basis of natural history stud- ies reported for the prelithium era (for example, Astrup, Epidemiology and Burden. Prevalence of nonbipolar depres- Fossum, and Holmboe 1959; Helgason 1964) to the postlithium sion has been estimated in a number of large-scale community era (for example, Goodwin and others 2003). epidemiological surveys. Lifetime prevalence estimates of hav- ing either major depressive disorder or dysthymia in these sur- veys are in the range 4.2 to 17.0 percent (Andrade and others Major Depressive Disorder 2003; Bijl and others 1998), with a weighted mean of 12.1 per- The core symptom of major depression is a disturbance of cent. Six- to 12-month prevalence estimates have a similarly mood; sadness is most typical, but anger, irritability, and loss of wide range (1.9 to 10.9 percent) (Andrade and others 2003; interest in usual pursuits may predominate. Often the affected Robins and Regier 1991), with a weighted mean of 5.8 percent. person is unable to experience pleasure (anhedonia) and may These wide differences in prevalence likely represent the difficul- feel hopeless. In many countries of the developing world, ties inherent in self-reporting of conditions that are invariably patients will not complain of such emotional symptoms, but stigmatized across cultures.Prevalence estimates are consistently rather of physical symptoms, such as fatigue or multiple aches highest in North America and lowest in Asia (with prevalence and pains. estimates of major depressive disorders generally a good deal Typical physiological symptoms that occur across cultures higher than those of dysthymia). include sleep disturbance (most often with early Epidemiological data document consistent delays in morning awakening, but occasionally excessive sleeping); patients initially seeking professional treatment for depression, appetite disturbance (usually loss of appetite and weight loss, especially among early-onset cases (Olfson and others 1998), as but occasionally excessive eating); and decreased energy. well as substantial undertreatment. For example, World Mental Behaviorally, some individuals with depression exhibit slowed Health surveys in six Western European countries found that motor movements (), whereas others only 36.6 percent of people with active nonbipolar depression may be agitated. Cognitive symptoms may include thoughts of in the 12 months before the survey received any professional worthlessness and guilt, suicidal thoughts, difficulty concen- treatment for this disorder during the subsequent year

610 | Disease Control Priorities in Developing Countries | Steven Hyman, Dan Chisholm, Ronald Kessler, and others (ESEMeD/MHEDEA 2000 Investigators 2004). The situation is depressive episode was a reduction in the duration of time even worse in developing countries, where the vast majority of depressed, equivalent to an increase in the remission rate (25 to people with depression who seek help do so in general health 40 percent improvement over no treatment; Malt and others care settings and complain of nonspecific physical symptoms. 1999; Solomon and others 1997). In addition, all interventions Such individuals receive a correct diagnosis in less than were attributed a modest improvement in the level of disability one-quarter of cases and typically are treated with of for an unremitted depressive episode (10 to 15 percent), doubtful efficacy (Linden and others 1999). resulting from increased proportions of cases moving from Depression is consistently found in community surveys to more to less severe health states. For the estimated 56 percent of be associated with substantial impairments in both productive prevalent cases eligible for maintenance treatment (at least two and social roles (Wang, Simon, and Kessler 2003). As with lifetime episodes), an additional effect of efficacious mainte- bipolar depression, but exacerbated by its high incidence, the nance treatment was incorporated into the analysis by reducing recurrent nature and disabling consequences of (unipolar) the incidence of recurrent episodes by 50 percent (Geddes and depression mean that overall disease burden estimates are high others 2003). Estimates of intervention effectiveness include the in all regions of the world (5,000 to 10,000 DALYs per 1 million positive change that would occur naturally and also incorporate population, as much as 5 percent of the total burden of disease any effect, which, in the treatment of depression, is not from all causes; table 31.1). Depression is, in fact, ranked as the inconsiderable (Andrews 2001). fourth leading cause of disease burden globally and represents the single largest contributor to nonfatal burden (Ustun and others 2004). ANXIETY DISORDERS

Interventions. Efficacy has been demonstrated for several Anxiety disorders are a group of disorders that have as their classes of antidepressant drugs and for two psychosocial treat- central feature the inability to regulate fear or worry. Although ments for depression (Paykel and Priest 1992). The older tri- anxiety in itself is likely to feature in the clinical presentation of cyclic (TCAs) and newer drugs, including the most patients, somatic complaints such as chest pain, palpita- selective serotonin reuptake inhibitors (SSRIs), have similar tions, respiratory difficulty, headaches, and the like are also efficacy. The newer drugs have milder side-effect profiles and common, and these symptoms may be more common in are consequently more likely to be tolerated at therapeutic developing countries. A number of different types of anxiety doses (Pereira and Patel 1999). SSRIs have not been widely used disorder exist, some of which are now briefly described. in developing countries because of their higher cost, although The central feature of panic disorder is an unexpected panic as the patent protection expires, this situation is likely to attack, which is a discrete period of intense fear accompanied change (Patel 1996). Of the psychosocial treatments with by physiologic symptoms such as a racing heart, shortness of demonstrated efficacy, the most widely accepted are cognitive- breath, sweating, or dizziness. The person may have an intense behavioral approaches. Alone or in combination, drug and psy- fear of losing control or of dying. Panic disorder is diagnosed chosocial treatments speed recovery from acute episodes. when panic attacks are recurrent and give rise to anticipatory Maintenance treatment with drugs decreases risk anxiety about additional attacks. People with panic disorder (Geddes and others 2003). Some evidence suggests that a may progressively restrict their lives to avoid situations in course of may also delay relapses. Although which panic attacks occur or situations from which it might be most of the clinical trials have been carried out in industrial difficult to escape should a occur. They common- countries, at least three high-quality trials have demonstrated ly avoid crowds, traveling, bridges, and elevators, and ultimate- the efficacy of antidepressants, group therapy, or both in devel- ly some individuals may stop leaving home altogether. oping countries (Araya and others 2003; Bolton and others Pervasive phobic avoidance is described as . 2003; Patel and others 2003). Generalized anxiety disorder is characterized by chronic For the cost-effectiveness analyses, depression was modeled unrealistic and excessive worry. These symptoms are accompa- as an episodic disorder with a high rate of remission and nied by specific anxiety-related symptoms such as sympathetic subsequent recurrence, and with excess mortality from suicide nervous system arousal, excessive vigilance, and motor tension. (Chisholm and others 2004). None of the selected depression Posttraumatic stress disorder follows serious trauma. It is interventions was accorded a reduction in case fatality, however, characterized by emotional numbness, punctuated by intrusive owing to the lack of robust clinical evidence that antidepressants reliving of the traumatic episode, generally initiated by envi- or psychotherapy in themselves alter the relative risk of death by ronmental cues that act as reminders of the trauma; by dis- suicide (Storosum and others 2001). The main modeled impact turbed sleep; and by hyperarousal, such as exaggerated startle of intervention targeted toward episodic treatment of a new responses.

Mental Disorders | 611 disorder (social )ischaracterizedbya disorder typically also have a second anxiety disorder, while persistent fear of social situations or performance situations that more than half the people with a history of either anxiety or expose a person to potential scrutiny by others. The affected typically have both types of disorder. person has intense fear that he or she will act in a way that will Retrospective reports from community surveys consistently be humiliating. Separating from show that anxiety disorders have early average ages of onset. extremes of normal temperament, such as shyness, is difficult. An impressive cross-national consistency can be seen in these Nonetheless, social anxiety disorder can be quite disabling. patterns, with an estimated median age of onset of anxiety at Simple phobias are extreme fear in the presence of discrete stim- approximately 15. uli or cues, such as fear of heights. Epidemiological surveys have also looked at the treatment The core features of obsessive-compulsive disorder are obses- of anxiety disorders. As with depression, consistent evidence in sions (intrusive, unwanted thoughts) and compulsions (per- these surveys suggests that delays in initially seeking profes- formance of highly ritualized behaviors intended to neutralize sional treatment for an anxiety disorder are widespread after the negative thoughts and resulting from the obses- first onset (Olfson and others 1998). This finding is especially sions). One symptom pattern might be repetitive hand washing true among early-onset cases. Epidemiological data also show beyond the point of skin damage to neutralize of that only a minority of current cases receive any formal treat- contamination. ment in Western countries, whereas treatment of anxiety disor- ders is virtually nonexistent in many developing countries. The most recently published surveys, the World Mental Health Natural History and Course surveys in six Western European countries, found that only The anxiety disorders differ in their age of onset, course of ill- 26.3 percent of people with an active anxiety disorder in the ness, and symptom triggers. One of these disorders, PTSD, is 12 months before the survey received any professional treat- dependent for its etiology on one or more powerfully negative ment (ESEMeD/MHEDEA 2000 Investigators 2004). life events. Although the anxiety disorders are discussed as a Anxiety disorders have consistently been found to be associ- group, panic disorder is chosen because of the available data for ated with substantial impairments in both productive roles (for the purposes of the cost-effectiveness analysis. example, work absenteeism, work performance, unemploy- Prevalence estimates of anxiety disorders based on commu- ment, and underemployment) and social roles (social isolation, nity epidemiological surveys vary widely, from a low of 2.2 per- interpersonal tensions, and marital disruption, among others) cent (Andrade and others 2003) to a high of 28.5 percent (see, for example, Kessler and Frank 1997). As noted earlier, for (Kessler and others 1994), with a weighted mean across surveys the purposes of this chapter, one of the anxiety disorders— of 15.6 percent. Prevalence estimates for anxiety disorders in panic disorder—has been chosen to describe interventions and the past 6 to 12 months have a similarly wide range (1.2 to undertake cost-effectiveness analysis. Panic disorder is as dis- 19.3 percent) (Andrade and others 2003; Kessler and others abling as obsessive-compulsive disorder and PTSD, accounts 1994), with a weighted mean of 9.4 percent. Despite wide for about one-third of all seriously impairing anxiety disorders, variation in overall prevalence, several clear relative prevalence is one of the most common anxiety disorders presenting for patterns can be seen across surveys. is generally treatment, and imposes an estimated burden of 600 to 800 the most prevalent lifetime anxiety disorder, with social phobia DALYs per 1 million population. generally the second most prevalent lifetime anxiety disorder. Good evidence exists that both drug and psychosocial Panic disorder and obsessive-compulsive disorder are generally treatments are effective for managing anxiety disorders. the least prevalent. Antidepressant drugs (both older TCAs and SSRIs) have been These surveys also provide evidence about the persistence of shown to be effective for the treatment of several anxiety disor- anxiety disorders, indirectly defined as the ratio of 6-month or ders, including panic disorder, reducing the duration and 12-month to lifetime prevalence. This ratio averages approxi- intensity of the disorder. Although high-potency benzodi- mately 60 percent for overall anxiety disorders, indicating a azepines are efficacious for panic disorder, these drugs carry a high rate of persistence across the life course. The highest risk of dependence and are not considered the first line of persistence is generally found for social phobia, and the lowest treatment. Psychosocial treatments, especially cognitive- for agoraphobia. These estimates of high persistence are con- behavioral therapy, are also effective in diminishing both panic sistent with results obtained from longitudinal studies of attacks and phobic avoidance. patients (Yonkers and others 2003). Anxiety disorders have consistently been found in epidemio- logical surveys to be highly comorbid both among themselves Interventions for Panic Disorder and with mood disorders (for example, de Graaf and others Although evidence-based interventions for panic disorder have 2003). The vast majority of people with a history of one anxiety yet to be evaluated or made widely available in developing

612 | Disease Control Priorities in Developing Countries | Steven Hyman, Dan Chisholm, Ronald Kessler, and others countries, the potential population-level impact of a number of (reflecting a societal preference for health benefits to be realized interventions—including older and newer antidepressants, sooner), but no age-weighting was used. anxiolytic drugs (benzodiazepines), and psychosocial Estimation of the baseline epidemiological situation that treatments—was examined. Interventions reduce the severity would prevail without treatment used incidence and preva- of panic attacks and improve the probability of making a full lence estimates from the Global Burden of Disease 2000 study recovery. Effect sizes for symptom improvement were drawn of the World Health Organization (WHO) (see online Global from a meta-analysis of the long-term effects of intervention of Burden of Disease documentation for the four disorders at panic disorder (Bakker and others 1998) and converted into an http://www.who.int/evidence/bod). Current pharmacolog- equivalent change in disability weight (Sanderson and others ical or psychosocial treatments do not exert a primary preven- 2004). Concerning remission, a number of controlled and tive effect on the onset of the four conditions (although naturalistic studies (for example, Faravelli, Paterniti, and some evidence exists that treating depression in parents may Scarpato 1995; Yonkers and others 2003) reveal a consistent reduce risk for offspring), indicating that currently observed remission rate of 12 to 13 percent for pharmacological and incidence rates coincide with those that would pertain under combination strategies—except for use, for no treatment. Prevention of recurrences of acute episodes (sec- which the evidence is that longer-term recovery is actually ondary prevention) has been demonstrated for maintenance worse than placebo (Katschnig and others 1995)—which repre- treatments for major depression and bipolar disorder. sents a 62 percent improvement in efficacy over the untreated Maintenance treatment with antipsychotic drugs decreases the remission rate (7.4 percent). risk of recurrent acute episodes of schizophrenia. For each con- dition, a range of treatment strategies was considered and assessed, including older (and widely available) psychothera- COST-EFFECTIVENESS METHODS AND RESULTS peutic drugs, newer pharmacotherapies, psychosocial treat- ments, and combination treatments (see table 31.2 for a list of This section estimates the burden attributed to schizophrenia, interventions included). bipolar disorder, depression, and panic disorder that could be averted (through scaling up) by proven, efficacious treatments. It is followed by calculations of the expected cost and cost- Estimation of Population-Level Treatment Costs effectiveness of such treatments. Analysis is conducted at the Cost estimation followed the principles and procedures level of six low- and middle-income geographical World Bank described in chapter 7 for carrying out economic analyses of dis- regions. ease control priorities in developing countries. For depression and panic disorder, treatment was assumed to occur in a pri- Estimation of Population-Level Effectiveness of Treatments mary care setting, whereas for schizophrenia and bipolar disor- In modeling the impact of mental health interventions, we der, which often produce highly disruptive behaviors, both hos- used a state-transition model (Lauer and others 2003) that pital- and community-based outpatient service models were traces the development of a population, taking into account derived and compared. Both program- and patient-level costs births, deaths, and the disease in question. In addition to pop- were identified and estimated. Program-level costs included the ulation size and structure, the model makes use of a number of infrastructure and administrative support for implementing epidemiological parameters (incidence and prevalence, remis- mental health treatments, as well as training inputs (for exam- sion, and cause-specific and residual rates of mortality) and ple, two to three days per trainee were estimated for training assigns age- and gender-specific disability weights to both the primary care doctors and case managers in psychotropic med- disease in question and the general population. The output of ication management). Patient-level resource inputs included the model is an estimate of the total healthy life years experi- medication regimens (for example, fluoxetine, 20 milligrams enced by the population over a lifetime period (100 years). The daily), laboratory tests (for example, lithium blood levels), model was run for a number of possible scenarios, including no primary care visits (including any contacts with a case manager), treatment at all (natural history), current treatment coverage, and hospital outpatient and inpatient care. Estimated patient- and scaled-up coverage of current as well as potential new level resource inputs for each of the four disorders were informed interventions. For the treatment scenarios, an implementation by empirical economic evaluative studies (for example, Patel and period of 10 years was used (thereafter, epidemiological rates others 2003;Srinivasa Murthy and others 2005) as well as a multi- and health state valuations return to natural history levels). The national Delphi consensus study of resource use for psychiatric model derived the number of additional healthy years gained disorders in seven developing countries (Ferri and others 2004). (equivalent to DALYs averted) each year in the population Region-specific unit costs or prices were applied to all resource compared with the outcome for no treatment at all. DALYs inputs (see Mulligan and others 2003) to give an annual cost for averted in future years were discounted at a rate of 3 percent each case as well as for all cases at the specified level of treatment

Mental Disorders | 613 Table 31.2 Interventions for Reducing the Burden of Major Psychiatric Disorders in Developing Countries

Disorder Intervention Example

Schizophrenia Older (neuroleptic) antipsychotic drug Haloperidol Treatment setting: hospital outpatient Newer (atypical) antipsychotic drug Treatment coverage (target): 80 percent Older antipsychotic drug and psychosocial treatment Haloperidol plus family Newer antipsychotic drug and psychosocial treatment Risperidone plus family psychoeducation Bipolar affective disorder Older mood-stabilizing drug Lithium carbonate Treatment setting: hospital outpatient Newer mood-stabilizing drug Sodium valproate Treatment coverage (target): 50 percent Older mood-stabilizing drug and psychosocial treatment Lithium plus family psychoeducation Newer mood-stabilizing drug and psychosocial treatment Valproate plus family psychoeducation Depression Episodic treatment Treatment setting: primary health care Older TCA Imipramine or amitriptyline Treatment coverage (target): 50 percent Newer antidepressant drug (SSRI; generic) Fluoxetine Psychosocial treatment Group psychotherapy Older antidepressant drug and psychosocial treatment Amitriptyline plus group psychotherapy Newer antidepressant drug and psychosocial treatment Fluoxetine plus group psychotherapy Maintenance treatment Older antidepressant drug and psychosocial treatment Imipramine plus group psychotherapy Newer antidepressant drug and psychosocial treatment Fluoxetine plus group psychotherapy Panic disorder Benzodiazepines Treatment setting: primary health care Older TCA Amitriptyline Treatment coverage (target): 50 percent Newer antidepressant drug (SSRI; generic) Fluoxetine Psychosocial treatment Older antidepressant drug and psychosocial treatment Amitriptyline plus cognitive therapy Newer antidepressant drug and psychosocial treatment Fluoxetine plus cognitive therapy

Source: Authors’ own estimates and recommendations. Note: Interventions in bold are the most cost-effective treatments of choice.

coverage. Costs incurred over the 10-year implementation peri- evidence-based pharmacological and psychosocial treatments od were discounted at 3 percent and expressed in U.S. dollars (Ferri and others 2004; Kohn and others 2004), plus those in (rather than international dollars, which attempt to adjust for contact with traditional healers (the effectiveness of which was differences in purchasing power between countries). conservatively approximated by ascribing a placebo effect size for each disorder).

Coverage In each World Bank region, treatment costs and effects were Results ascribed to the population in need, both at current levels Tables 31.3 through 31.6 provide estimates of the population- of intervention coverage and at a scaled-up, target level of level effects (measured in DALYs averted), costs, and cost- coverage (80 percent for schizophrenia, 50 percent for the other effectiveness of each intervention by world region for the four conditions). Target coverage levels were predicated on the basis types of psychiatric disorder considered in this chapter. A num- of what could feasibly be achieved given existing rates of treat- ber of key findings emerge from this analysis. ment (Ferri and others 2004; Kohn and others 2004), as well as on prerequisites for increased coverage, such as recognition of Treatment Effectiveness. Results for schizophrenia and bipo- common mental disorders in primary care. Estimation of cur- lar disorder are similar (albeit at differing coverage levels), rang- rent regional levels of effective coverage is hampered by lack of ing from less than 100 DALYs averted per 1 million population data; nevertheless, an attempt was made to approximate the under the current situation in Sub-Saharan Africa and South expected proportion of the diseased population receiving Asia to 350 to 400 DALYs averted per 1 million population for

614 | Disease Control Priorities in Developing Countries | Steven Hyman, Dan Chisholm, Ronald Kessler, and others Table 31.3 Cost-Effectiveness Results: Schizophrenia

Model definition: World Bank region Treatment setting: (a) hospital- based; (b) community-based Sub-Saharan Latin America Middle East and Europe and East Asia and Treatment coverage: 80 percent Africa and the Caribbean North Africa Central Asia South Asia the Pacific Total effect (DALYs averted per year per 1 million population) Current situation 74 136 115 258 87 148 Older (neuroleptic) antipsychotic drug 149 219 214 254 177 231 Newer (atypical) antipsychotic drug 160 235 230 273 190 248 Older antipsychotic drug plus 254 373 364 353 300 392 psychosocial treatment Newer antipsychotic drug plus 261 383 373 364 308 403 psychosocial treatment Total cost (US$ million per year per 1 million population) Current situation 0.42 2.07 1.31 3.13 0.51 1.11 Hospital-based service model Older (neuroleptic) antipsychotic drug 0.60 3.09 2.40 2.24 0.74 1.18 Newer (atypical) antipsychotic drug 2.80 6.33 5.41 6.16 3.36 4.63 Older antipsychotic drug plus 0.67 3.27 2.56 2.36 0.81 1.26 psychosocial treatment Newer antipsychotic drug plus 2.87 6.56 5.61 6.31 3.44 4.73 psychosocial treatment Community-based service model Older (neuroleptic) antipsychotic drug 0.40 1.58 1.42 1.17 0.44 0.66 Newer (atypical) antipsychotic drug 2.59 4.85 4.45 5.11 3.07 4.12 Older antipsychotic drug plus 0.47 1.81 1.61 1.32 0.52 0.75 psychosocial treatment Newer antipsychotic drug plus 2.67 5.09 4.66 5.28 3.16 4.22 psychosocial treatment Cost-effectiveness (US$ per DALY averted) Current situation 5,695 15,192 11,400 12,134 5,900 7,533 Hospital-based service model Older (neuroleptic) antipsychotic drug 4,047 14,123 11,205 8,793 4,164 5,120 Newer (atypical) antipsychotic drug 17,433 26,893 23,543 22,530 17,702 18,700 Older antipsychotic drug plus 2,623 8,781 7,040 6,685 2,693 3,212 psychosocial treatment Newer antipsychotic drug plus 10,996 17,146 15,027 17,329 11,164 11,746 psychosocial treatment Community-based service model Older (neuroleptic) antipsychotic drug 2,668 7,230 6,618 4,595 2,499 2,855 Newer (atypical) antipsychotic drug 16,174 20,583 19,352 18,685 16,178 16,622 Older antipsychotic drug plus 1,839 4,847 4,431 3,745 1,743 1,917 psychosocial treatment Newer antipsychotic drug plus 10,232 13,313 12,485 14,481 10,239 10,484 psychosocial treatment

Source: Authors’ own estimates. Note: Intervention data in bold are the most cost-effective treatments of choice.

Mental Disorders | 615 Table 31.4 Cost-Effectiveness Results: Bipolar Disorder

Model definition: World Bank region Treatment setting: (a) hospital- based; (b) community-based Sub-Saharan Latin America Middle East and Europe and East Asia and Treatment coverage: 50 percent Africa and the Caribbean North Africa Central Asia South Asia the Pacific Total effect (DALYs averted per year per 1 million population) Current situation 79 128 97 199 93 153 Older mood-stabilizing drug (lithium) 292 336 296 381 319 389 Newer mood-stabilizing drug 211 300 273 331 278 351 (valproate) Older mood-stabilizing drug plus 312 365 322 413 346 422 psychosocial treatment Newer mood-stabilizing drug plus 232 330 300 365 306 386 psychosocial treatment Total cost (US$ million per year per 1 million population) Current situation 0.31 1.22 0.74 1.27 0.42 0.67 Hospital-based service model Older mood-stabilizing drug (lithium) 0.61 2.77 1.92 2.03 0.82 1.30 Newer mood-stabilizing drug 0.79 2.87 2.04 2.20 1.03 1.53 (valproate) Older mood-stabilizing drug plus 0.63 2.79 1.95 2.05 0.84 1.32 psychosocial treatment Newer mood-stabilizing drug plus 0.81 2.90 2.08 2.22 1.06 1.55 psychosocial treatment Community-based service model Older mood-stabilizing drug (lithium) 0.46 1.78 1.20 1.37 0.59 0.93 Newer mood-stabilizing drug 0.64 1.91 1.36 1.57 0.82 1.17 (valproate) Older mood-stabilizing drug plus 0.48 1.80 1.23 1.39 0.62 0.95 psychosocial treatment Newer mood-stabilizing drug plus 0.67 1.95 1.39 1.59 0.85 1.19 psychosocial treatment Cost-effectiveness (US$ per DALY averted) Current situation 3,967 9,518 7,668 6,398 4,463 4,373 Hospital-based service model Older mood-stabilizing drug (lithium) 2,091 8,246 6,478 5,341 2,553 3,348 Newer mood-stabilizing drug 3,727 9,579 7,501 6,648 3,709 4,358 (valproate) Older mood-stabilizing drug plus 2,016 7,644 6,036 4,957 2,424 3,119 psychosocial treatment Newer mood-stabilizing drug plus 3,480 8,800 6,937 6,100 3,459 4,016 psychosocial treatment Community-based service model Older mood-stabilizing drug (lithium) 1,587 5,295 4,068 3,608 1,862 2,394 Newer mood-stabilizing drug 3,057 6,386 4,971 4,727 2,943 3,338 (valproate) Older mood-stabilizing drug plus 1,545 4,928 3,823 3,359 1,787 2,241 psychosocial treatment Newer mood-stabilizing drug plus 2,874 5,908 4,645 4,359 2,765 3,092 psychosocial treatment

Source: Authors’ own estimates. Note: Intervention data in bold are the most cost-effective treatments of choice.

616 | Disease Control Priorities in Developing Countries | Steven Hyman, Dan Chisholm, Ronald Kessler, and others Table 31.5 Cost-Effectiveness Results: Depression

Model definition: World Bank region Treatment setting: primary health care Sub-Saharan Latin America Middle East and Europe and East Asia and Treatment coverage: 50 percent Africa and the Caribbean North Africa Central Asia South Asia the Pacific Total effect (DALYs averted per year per 1 million population) Current situation 133 264 218 308 218 243 Episodic treatment: older 599 995 920 874 987 891 antidepressant drug (TCA) Episodic treatment: newer 632 1,049 971 925 1,042 941 antidepressant drug (SSRI) Episodic psychosocial treatment 624 1,036 958 936 1,028 927 Episodic psychosocial treatment 745 1,237 1,144 1,100 1,228 1,107 plus older antidepressant Episodic psychosocial treatment 745 1,237 1,144 1,100 1,228 1,107 plus newer antidepressant Maintenance psychosocial treatment 1,174 1,953 1,806 1,789 1,937 1,747 plus older antidepressant Maintenance psychosocial treatment 1,174 1,953 1,806 1,789 1,937 1,747 plus newer antidepressant Total cost (US$ million per year per 1 million population) Current situation 0.36 0.90 0.63 0.74 0.56 0.67 Episodic treatment: older 0.30 1.28 0.96 0.81 0.47 0.47 antidepressant drug (TCA) Episodic treatment: newer 0.66 1.86 1.47 1.39 1.04 0.99 antidepressant drug (SSRI) Episodic psychosocial treatment 0.37 1.67 1.27 0.97 0.55 0.53 Episodic psychosocial treatment 0.50 1.96 1.53 1.21 0.77 0.72 plus older antidepressant Episodic psychosocial treatment 0.90 2.60 2.10 1.85 1.40 1.29 plus newer antidepressant Maintenance psychosocial treatment 0.96 3.44 2.77 2.19 1.45 1.38 plus older antidepressant Maintenance psychosocial treatment 1.80 4.80 3.99 3.56 2.81 2.59 plus newer antidepressant Cost-effectiveness (US$ per DALY averted) Current situation 2,692 3,414 2,905 2,391 2,546 2,777 Episodic treatment: older 505 1,288 1,039 929 478 533 antidepressant drug (TCA) Episodic treatment: newer 1,042 1,771 1,516 1,501 1,003 1,048 antidepressant drug (SSRI) Episodic psychosocial treatment 592 1,611 1,330 1,035 537 570 Episodic psychosocial treatment 674 1,586 1,335 1,104 627 653 plus older antidepressant Episodic psychosocial treatment 1,203 2,101 1,834 1,682 1,140 1,161 plus newer antidepressant Maintenance psychosocial treatment 817 1,760 1,533 1,226 749 788 plus older antidepressant Maintenance psychosocial treatment 1,535 2,459 2,211 1,990 1,449 1,481 plus newer antidepressant

Source: Authors’ own estimates. Note: Intervention data in bold are the most cost-effective treatments of choice.

Mental Disorders | 617 Table 31.6 Cost-Effectiveness Results: Panic Disorder

Model definition: World Bank region Treatment setting: primary health care Sub-Saharan Latin America Middle East and Europe and East Asia and Treatment coverage: 50 percent Africa and the Caribbean North Africa Central Asia South Asia the Pacific Total effect (DALYs averted per year per 1 million population) Current situation 49 94 64 88 57 90 Anxiolytic drug (benzodiazepine) 144 182 170 183 168 195 Older antidepressant drug (TCA) 232 290 272 290 269 312 Newer antidepressant drug (SSRI; 245 307 287 307 284 330 generic) Psychosocial treatment 233 292 273 292 270 313 (cognitive-behavioral therapy) Older antidepressant plus 262 329 308 329 304 353 psychosocial treatment Newer antidepressant plus 276 346 324 346 320 372 psychosocial treatment Total cost (US$ million per year per 1 million population) Current situation 0.06 0.13 0.08 0.07 0.05 0.10 Anxiolytic drug (benzodiazepine) 0.10 0.20 0.15 0.15 0.10 0.12 Older antidepressant drug (TCA) 0.09 0.18 0.14 0.14 0.08 0.11 Newer antidepressant drug 0.15 0.27 0.21 0.23 0.16 0.20 (SSRI; generic) Psychosocial treatment (cognitive- 0.11 0.27 0.21 0.17 0.09 0.11 behavioral therapy) Older antidepressant plus 0.15 0.32 0.26 0.23 0.13 0.17 psychosocial treatment Newer antidepressant plus 0.22 0.41 0.34 0.32 0.22 0.26 psychosocial treatment Cost-effectiveness (US$ per DALY averted) Current situation 1,192 1,378 1,208 824 948 1,109 Anxiolytic drug (benzodiazepine) 681 1,075 892 842 572 629 Older antidepressant drug (TCA) 369 619 508 474 305 339 Newer antidepressant drug (SSRI; 630 865 747 741 567 606 generic) Psychosocial treatment (cognitive- 468 927 786 594 338 365 behavioral therapy) Older antidepressant plus 556 977 844 685 443 474 psychosocial treatment Newer antidepressant plus 788 1,188 1,050 918 671 709 psychosocial treatment

Source: Authors’ own estimates. CBT cognitive behavioral therapy Note: Intervention data in bold are the most cost-effective treatments of choice. combination drug and psychosocial interventions in Europe tolerability and adherence); lithium was considered modestly and Central Asia and East Asia and the Pacific. Second- more effective as a mood-stabilizing drug than valproate (on the generation (atypical) antipsychotic drugs were considered basis of its additional positive effect on suicide rates). Adjuvant slightly more effective than first-generation drugs (on the basis psychosocial treatment in combination with pharmacotherapy of a modest intrinsic efficacy difference and differences in significantly added to expected population-level health gain.

618 | Disease Control Priorities in Developing Countries | Steven Hyman, Dan Chisholm, Ronald Kessler, and others With the exception of Europe and Central Asia, less than 10 per- program using newer antidepressants, three times more costly cent of the disease burden currently is being averted,whereas the than episodic treatment with newer antidepressant drugs only. implementation of combined interventions at a scaled-up level Patient-level resource inputs for panic disorder interventions ofcoverageisexpectedtoavert14to22percentoftheburdenof cost US$50 to US$200 per case per year, and overall costs schizophrenia (coverage level, 80 percent) and 17 to 29 percent including program costs of training and administration of the burden of bipolar disorder (coverage level, 50 percent). amounted to US$0.10 to US$0.30 per capita. For primary care treatment of common mental disorders, including depression and panic disorder, current levels of effec- Cost-Effectiveness. Compared with both the current situation tive coverage avert only 3 to 8 percent of the existing disease and the epidemiological situation of no treatment (natural his- burden, whereas scaling up of the most effective interventions tory), the most cost-effective strategy for averting the burden of to a coverage level of 50 percent could be expected to avert psychosis and severe affective disorders in developing countries more than 20 percent of the burden of depression and up to is expected to be a combined intervention of first-generation one-third of the burden of panic disorder. Considered at a pop- antipsychotic or mood-stabilizing drugs with adjuvant psy- ulation level, episodic treatments for depressive episodes did chosocial treatment delivered through a community-based not differ substantially within regions (averting 10 to15 percent outpatient service model, with a cost-effectiveness ratio of of current burden); more substantial health gain is expected below US$2,000 in Sub-Saharan Africa and South Asia, rising by providing maintenance treatment to individuals with recur- to US$5,000 in Latin America and the Caribbean (equivalent to rent depression (approximately 1,200 to 1,900 DALYs averted more than 500 DALYs averted per US$1 million expenditure in per 1 million population; 18 to 23 percent of burden). Such an Sub-Saharan Africa and South Asia and 200 DALYs averted in approach has been found to reduce the risk of relapse by half. Latin America and the Caribbean). Currently, the high acquisi- Although the evidence to date from developing regions is mea- tion price of second-generation antipsychotic drugs makes ger, our results suggest that SSRIs such as fluoxetine, alone or in their use in developing regions questionable on efficiency combination with psychosocial treatment, are the most effec- grounds, although this situation can be expected to change as tive treatments for panic disorder, with health gains consider- these drugs come off patent. By contrast, evidence indicates ably better than those estimated for benzodiazepine anxiolytic that the relatively modest additional cost of adjuvant psy- drugs such as alprazolam. chosocial treatment reaps significant health gains, thereby making such a combined strategy for schizophrenia and Treatment Costs. Community-based service models for bipolar disorder treatment more cost-effective than pharma- schizophrenia and bipolar disorder were found to be apprecia- cotherapy alone. bly less costly than hospital-based service models (for example, For more common mental disorders treated in primary care interventions for bipolar disorder were 25 to 40 percent less settings (depressive and anxiety disorders), the single most costly). The total cost per capita of community-based outpa- cost-effective strategy is the scaled-up use of older antidepres- tient treatment with first-generation antipsychotic or mood- sants (because of their lower cost but similar efficacy compared stabilizing drugs, including all patient-level resource needs as with newer antidepressants). However, as the price margin well as infrastructural support, ranged from US$0.40 to between older and generic newer antidepressants continues to US$0.50 in Sub-Saharan Africa and South Asia to US$1.20 to diminish, generic SSRIs—which have milder side effects and US$1.90 in Latin America and the Caribbean and in Europe are more likely to be taken at a therapeutic dose (Pereira and and Central Asia (equivalent patient costs per year, US$170 to Patel 1999)—can be expected to be at least as cost-effective US$300 and US$300 to US$800, respectively). The cost per and, therefore, the pharmacological treatment of choice in the capita for interventions using second-generation (atypical) future. Because depression is often a recurring condition, antipsychotic drugs still under patent is much higher (US$2.50 proactive care management, including long-term maintenance to US$5.00). By contrast, some of the newer antidepressant treatment with antidepressant drugs, represents a cost-effective drugs (SSRIs) are now off patent, and their use in treating way of significantly reducing the enormous burden of depres- depression and panic disorder was accordingly costed at their sion that exists in developing regions now (400 to 1,300 DALYs generic, nonbranded price. The patient-level cost of treating a averted per US$1 million expenditure). 6-month episode of depression ranged from as little as US$30 (older antidepressants in Sub-Saharan Africa or South Asia) to US$150 (newer antidepressants in combination with brief psy- POLICY AND SERVICE IMPLICATIONS chotherapy in Latin America and the Caribbean). Total annual costs for all incidents of depressive episodes receiving treat- Many attempts have been made during the past 50 years to ment, including training and other program-level costs, were as have mental health care placed higher on national and interna- much as US$2 to US$5 per capita for a maintenance treatment tional agendas. In 1974, a WHO Expert Committee on the

Mental Disorders | 619 Organization of Mental Health Services in Developing work closely (and apparently effectively) with conventional Countries (WHO 1975) made the following recommendations: mental health services (Thara,Padmavati,and Srinivasan 2004). Alternatively, animosity and competition can exist, and recent • Develop a national mental health policy and create a unit examples of human rights violations by traditional healers within the Health Ministry to implement it. demonstrate the heterogeneity of this group of providers. • Budget for workforce development, essential drug procure- The formal diagnosis and treatment of mental disorders ment, infrastructure development, data collection, and occur in both primary and specialist health services. Examples research. in nearly a dozen countries now show it is feasible and practi- • Decentralize service provision and integrate mental health cable to treat common mental disorders in primary health care into primary health care. settings (for example, Chisholm and others 2000; De Jong • Train and supervise primary health care providers in mental 1996; Mohit and others 1999). The challenge is to enhance sys- health using specialist mental health staff. tems of care by taking effective local models and disseminating them throughout a country. Thirty years later, international agencies, nongovernmental Concern has been expressed that the more sophisticated organizations, and professional bodies continue to make those used in mental health care are beyond the exact recommendations. One reason for the lack of action in human resources of developing countries. However, basic psy- mental health has been the paucity of information on the cost- chological therapies can be effective, though there is some evi- effectiveness of mental health interventions. Advocacy without dence, at least for depression, that the newer drug therapies are the necessary can readily be ignored in countries with more cost-effective than psychological therapies (Patel and massive health problems and meager resources. This chapter others 2003). Psychoeducational family intervention has been aims to address this deficiency. shown to be suitable for rehabilitation in schizophrenia in rural Symptoms of mental disorders are often attributed to other China (Ran and others 2003) and to be cost-effective compared illnesses, and mental disorders are often not considered health with other standard treatment (Xiong and others 1994). problems (Jacob 2001). Many nonscientific explanations for Evidence also shows that nurses can replace physicians as pri- mental illness exist, and stigma exists to varying degrees every- mary health care providers in certain circumstances without where (Weiss and others 2001) with widespread delays or fail- loss of effectiveness (Climent and others 1978). Primary care ure to seek appropriate care (James and others 2002). practitioners need support to develop skills and experience in When care is sought, a hierarchy of interventions comes into diagnosing and treating mental disorders: they need a sustain- play, ranging from self-help, informal community support, tra- able supply of medicines, access to supervision, and incentives ditional healers, primary health care, specialist community to see patients with mental illness (Abas and others 2003). mental health care, and psychiatric units in general hospitals to Community approaches using low-cost, locally available specialist long-stay mental hospitals. The mix of interventions resources may improve treatment adherence and clinical out- depends on the availability of resources within a country or comes even in rural and underresourced settings (Chatterjee region (Saxena and Maulik 2003). The more resource- and others 2003; Srinivasa Murthy and others 2005). constrained the country or region is, the greater is the reliance In most countries, acute inpatient beds are being moved on self-help, informal community support (especially family- from mental hospitals into general or district hospitals. based), and primary health care. Although this policy potentially improves accessibility and Traditional healers are often the first source individuals with increases the links with, and support provided to, primary mental illness and their families turn to for professional assis- mental health care, concerns can be raised as to whether gen- tance (see, for example,Abiodun 1995).A recent review of com- eral hospitals can adapt to provide adequate services to people mon mental disorders among primary health and tradi- with severe mental disorders. However, such services have tional healers in urban Tanzania showed that the prevalence of been effectively established in a number of countries (see, for common mental disorders among those attending traditional example, Alem and others 1999; Kilonzo and Simmons 1998), healers was double that of patients at primary health care centers showing this form of service delivery to be feasible when it is (Ngoma, Prince, and Mann 2003). Traditional healers are a het- clinically indicated. erogeneous group and include faith healers, spiritual healers, Nongovernmental organizations are important providers of religious healers, and practitioners of indigenous or alternative mental health care. An estimated 93 percent of African and systems of medicine. In some countries, they are part of the 80 percent of Southeast Asian countries have nongovernmental informal health sector,but in other countries,traditional healers organizations in the mental health sector. They provide diverse charge for their services and should be considered part of the services—including advocacy, informal support, housing, private health care sector. Often, traditional healers have high , substance misuse counseling, acceptability and are accessible; at times, traditional healers support, rehabilitation, research, and other programs—that

620 | Disease Control Priorities in Developing Countries | Steven Hyman, Dan Chisholm, Ronald Kessler, and others complement, or in some cases substitute for, public and private developing countries (Tansella and Thornicroft 1998; clinical services (Levkoff, Macarthur, and Bucknall 1995; Patel Townsend and others 2004; WHO 2003). and Thara 2003). Services for children and adolescents, the majority of the population in many developing countries, are even more defi- CONCLUSION: PUBLIC SUPPORT FOR A cient than those for adults. Priority needs to be given to these COST-EFFECTIVE INTERVENTION PACKAGE services (Rahman and others 2000). At the other end of the life spectrum, many developing countries are facing aging popula- In developing countries, much of the mental health care spend- tions with grossly underdeveloped aged care services (Levkoff, ing is reported to be out of pocket. Individuals purchase mod- Macarthur, and Bucknall 1995). The high level of civil conflict ern and traditional treatments if they can afford to do so. and natural disasters requires attention to postconflict and Although a large private health sector exists in low-income posttrauma mental health conditions. The prevalence of these countries (Mills and others 2002), the quality and cost vary. disorders is demonstrated by a recent study (Livanou, Basoglu, Although unregulated markets fail in health, they fail even and Kalendar 2002) showing that, of 1,000 survivors of the more in mental health. It is unlikely that a country will be able August 1999 earthquake in Turkey, the incidence of PTSD was to rely on an unregulated private sector to deliver services that 63 percent and of depression was 42 percent. will reduce the burden of mental disorders. Specialist mental health providers, especially mental hospi- In addition to being a large and growing component of dis- tals, tend to focus the services they provide on the lower- ease burden, mental disorders meet virtually all the criteria by prevalence, higher-disability disorders, such as schizophrenia which we determine the need for government involvement in and bipolar disorder. Modern treatments, if available and used, health care (Beeharry and others 2002). They affect the poor, allow most patients to be treated effectively out of hospital. cause externalities, and inflict catastrophic costs; moreover, pri- Specifically, the use of antipsychotic and mood-stabilizing vate demand is inadequate. Indeed, the authors recognize that drugs and the development of strategies for community-based the main measure of outcome used in this and other chapters— treatment have led to the closing of large numbers of psychi- the disability-adjusted life year—is limited to capturing change atric inpatient beds in many countries and their replacement in service user–level symptoms, disability, recovery, and case- with community services and general hospital psychiatric units fatality. The DALY does not capture the positive change that (for example, Larrobla and Botega 2001). treatment may have on a number of other significant conse- However, in some countries, the majority of psychotic quences of mental disorders, including family burden (in par- patients remain in long-term inpatient facilities that engage in ticular, productive time and household resources given up in custodial care, which is often of poor quality; moreover, basic the care of the sick family member) and lost productivity, at the rights are often violated at such facilities (van Voren and level of both the individual and the household (treatment accel- Whiteford 2000). Even if the quality of care is reasonable, acces- erates return to paid work or usual household activities) and, by sibility is a problem: these hospitals are often situated in urban implication, at the level of society in general. The evidence base areas, but populations are largely rural and have limited trans- for these productivity increases, although modest in volume, portation (Saraceno and others 1995). Furthermore, the con- constitutes an important additional argument alongside “cost centration of resources in these facilities can leave little for per DALY” considerations for investing in mental health. other service components (Gallegos and Montero 1999). For The total budgetary requirements and health consequences example, in Indonesia, 97 percent of the mental health budget of a cost-effective package of mental health care can begin to be is spent on public mental hospitals (Trisnantoro 2002). For mapped out by selecting one intervention for each of the four many developing countries, the debate about the role of, or disorders considered in this chapter. Although the data avail- problems with, mental hospitals is subsumed within a gross able for this exercise have limitations and will need to be refined deficiency of psychiatric beds of any kind. with further research, table 31.7 summarizes the estimated The priority for virtually all countries is generating suffi- costs and effects of a package consisting of (a) outpatient-based cient resources for primary mental health care and deciding treatment of schizophrenia and bipolar disorder with first-gen- how to expand and best use scarce specialist resources. The eration antipsychotic or mood-stabilizing drugs and adjuvant quality of care is often very poor, and huge variations exist in psychosocial treatment, (b) proactive care of depression in pri- resource availability between countries (Saxena and Maulik mary care with generic SSRIs (including maintenance treat- 2003; WHO 2001). Very few countries have what could be con- ment of recurrent episodes), and (c) treatment of panic disor- sidered an optimal mix of these services, and there are no uni- der in primary care with generic SSRIs. The estimated benefit of versally accepted planning parameters. However, conceptual such a package would be an annual reduction of 2,000 to 3,000 models for developing national mental health policy and DALYs per 1 million population, at a cost of US$3 million to guidelines for service planning exist that can be useful in US$9 million (that is, US$3 to US$4 per capita in Sub-Saharan

Mental Disorders | 621 Table 31.7 Costs and Effects of a Specified Mental Health Care Package

World Bank region Sub-Saharan Latin America Middle East and Europe and East Asia and Africa and the Caribbean North Africa Central Asia South Asia the Pacific Total effect (DALYs averted per year per 1 million population) Schizophrenia: older antipsychotic drug plus 254 373 364 353 300 392 psychosocial treatment Bipolar disorder: older mood-stabilizing drug 312 365 322 413 346 422 plus psychosocial treatment Depression: proactive care with newer 1,174 1,953 1,806 1,789 1,937 1,747 antidepressant drug (SSRI; generic) Panic disorder: newer antidepressant drug 245 307 287 307 284 330 (SSRI; generic) Total effect of interventions 1,985 2,998 2,779 2,862 2,867 2,891 Total cost (US$ million per year per 1 million population) Schizophrenia: older antipsychotic drug 0.47 1.81 1.61 1.32 0.52 0.75 plus psychosocial treatment Bipolar disorder: older mood-stabilizing drug 0.48 1.80 1.23 1.39 0.62 0.95 plus psychosocial treatment Depression: proactive care with newer 1.80 4.80 3.99 3.56 2.81 2.59 antidepressant drug (SSRI; generic) Panic disorder: newer antidepressant drug 0.15 0.27 0.21 0.23 0.16 0.20 (SSRI; generic) Total cost of interventions 2.9 8.7 7.0 6.5 4.1 4.5 Cost-effectiveness (DALYs averted per US$1 million expenditure) Schizophrenia: older antipsychotic drug 544 206 226 267 574 522 plus psychosocial treatment Bipolar disorder: older mood-stabilizing drug 647 203 262 298 560 446 plus psychosocial treatment Depression: proactive care with newer 652 407 452 502 690 675 antidepressant drug (SSRI; generic) Panic disorder: newer antidepressant drug 1,588 1,155 1,339 1,350 1,765 1,649 (SSRI; generic)

Source: Authors’ own estimates.

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